Arthritis is a debilitating disease that afflicts millions of people, and for which there currently are no cures. Several forms of arthritis are known. Rheumatoid arthritis is characterized as a chronic systemic inflammatory disease, primarily of the joints, and generally marked by inflammatory changes in the synovial membranes and articular structures and by atrophy and rarefaction of the bones. Osteoarthritis is a noninflammatory degenerative joint disease occurring most often in older persons. It is characterized by degeneration of the articular cartilage, hypertrophy of bone at the margins, and changes in the synovial membrane. Pain and stiffness accompany it, particularly after prolonged physical activity. Osteoarthritis is also referred to as degenerative arthritis, hypertrophic arthritis, and degenerative joint disease. The exact cause of arthritis is still unknown, and there are no cures. The current treatments are designed to relieve the pain, and to diminish the symptoms that accompany the disease. Most of the known treatments are anti-inflammatory agents such as nonsteroidal anti-inflammatory agents (NSAIDs) and cyclooxygenase (COX) inhibitors. Many of these agents, especially the NSAIDs, cause severe side effects such as gastrointestinal damage, thus limiting their clinical use. Several compounds that inhibit a specific cyclooxygenase enzyme, namely cyclooxygenase-2 (COX-2), have been recently developed and are said to have fewer adverse side effects. Because arthritis is such a debilitating disease, especially for an aging population over 50, the need continues for better and more effective agents that reduce the pain and suffering of arthritis, and have few or no side effects.
There has now been discovered a series of substituted furanones that are potent anti-arthritic agents, and are especially effective for inhibiting the pain that accompanies arthritis. Ducharme et al., in U.S. Pat. No. 5,474,995, disclose several thiophene, isothiazole and furan compounds that can be substituted with groups such as phenyl and alkyl. The compounds are said to be cyclooxygenase inhibitors, and as such, are said to be effective in treating various forms of pain, and inflammatory diseases, including arthritis. The reference fails to describe or suggest furanones having aminoalkyl and carboxy alkyl substituents as now required. An object of this invention is to provide new chemical compounds characterized as being substituted furanones, pharmaceutical formulations containing such furanones, and a method for treating arthritis and pain by administering such furanones.